Actinic keratoses



Actinic keratoses


Sherrif F. Ibrahim and Marc D. Brown


Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports


image


Actinic keratoses (AK) are ill-defined pink to skin-colored, scaly papules found on chronically sun-exposed areas in light-skinned individuals. They most frequently appear on the face, ears, balding scalp, extensor forearms, and dorsal hands. AKs are a strong predictor for the development of squamous cell carcinoma (SCC) and, to a lesser extent, basal cell carcinoma. Australians have the highest reported prevalence, which approaches 60%, and in the US AKs are the second most common reason for visits to the dermatologist.



Management strategy


Actinic keratoses are common dysplastic intra-epidermal lesions that are considered to be precursors to SCC. Reports have varied as to the rates of progression to invasive SCC, from 0.025% to over 25% per year, and AKs are commonly located adjacent to SCC histologically. For these reasons, most practitioners advocate the treatment of AKs, as considerable morbidity and potential mortality can be associated with invasive disease. However, there have been no randomized controlled studies demonstrating a reduction in the frequency of SCC with treatment of AKs.


The diagnosis of AK is primarily clinical, and because of their superficial nature, a variety of effective management approaches exist. Biopsy of suspected AKs is typically not warranted; however, in patients with a history of multiple skin cancers, immunosuppressed patients, and lesions in high-risk areas such as the lip or ear, clinicians should have a low threshold for biopsy to rule out invasive SCC. Indications for biopsy include tenderness, rapid growth or thickening of lesions, bleeding, hyperkeratosis, and failure to respond to treatment.


Prevention of AKs through sun avoidance and diligent use of broad-spectrum sunscreens and blocking agents is an important aspect of management. This has been shown to prevent the development of new AKs and reduce the incidence of non-melanoma skin cancers.


With cumulative sun exposure and advancing age, rates of AK development increase, necessitating either ablative or topical treatment. Cryotherapy with liquid nitrogen is by far the most commonly employed therapeutic modality because it can be performed quickly and effectively in the office setting. However, given the common appearance of AKs on a background of diffuse actinic damage, individual lesions may be poorly defined and involve large, contiguous areas requiring field treatment with topical agents such as 5-fluorouracil (5-FU) or imiquimod. The latter has recently been shown to have high rates of treatment success with durable results and has become an accepted first-line therapy with a newer 3.75% formulation recently introduced. A novel agent, ingenol mebutate, is derived from the Euphorbia peplus plant and has been approved as an additional topical agent for the field treatment of AKs. The advantages of topical approaches are that they are patient-administered, non-invasive, carry little risk of scarring or pigmentary change, and can be used for anatomically difficult or cosmetically sensitive areas. However, these agents require adequate patient compliance and are often accompanied by prolonged erythema lasting several weeks. Photodynamic therapy (PDT) with aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) has continued to become more widespread, given its proven therapeutic results and excellent cosmetic outcome. PDT offers a physician-administered approach to field treatment with shorter periods of inflammation and erythema than several topical agents, and thus many studies indicate higher patient satisfaction. Variations in the light dose, light source, sensitizing agent and its application time, and frequency of treatments may improve efficacy. Head-to-head trials of different treatment approaches are difficult to perform, as variations in treatment protocols make direct comparisons challenging. Recently, there has been a growing trend towards combination therapy, such as topical agents either before or after cryotherapy, or sequential use of multiple topical modalities with varying mechanisms of action. Other approaches such as laser resurfacing, chemical peels, and dermabrasion may be considered in certain situations when lesions have failed the above treatments, or if severe photodamage is present. Finally, for recalcitrant or hyperkeratotic lesions, curettage or excision may be appropriate.



Specific investigations


In selected cases:









First-line therapies





















imageSunscreens A
imageCryosurgery B
imageTopical 5-FU A
imageImiquimod A
imagePhotodynamic therapy A









Effect of a 1 week treatment with 0.5% topical fluorouracil on occurrence of actinic keratosis after cryosurgery.

Jorizzo J, Weiss J, Furst K, VandePol C, Levy SF. Arch Dermatol 2004; 140: 813–16.


This study demonstrates that there is a role for the combination of therapeutic modalities in the treatment of AKs. In this prospective, double-blind, randomized controlled trial, 144 patients, each with at least five AKs on the face, were randomized to receive 1 week of treatment with 0.5% 5-FU cream daily for 7 days or placebo cream. Patients were then treated with single freeze–thaw cycle cryotherapy using liquid nitrogen, with a thaw time of 10 seconds. These patients were then followed up at 4 weeks and 6 months. The authors found that, at 4 weeks, 16.7% of patients in the 5-FU group were completely clear of lesions, compared to 0% in the vehicle group (p<0.001). At 6 months post-treatment, 30% of patients in the 5-FU group were clear of lesions, compared to 7.7% of patients in the vehicle group (p<0.001).

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Aug 7, 2016 | Posted by in Dermatology | Comments Off on Actinic keratoses

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